For more information on the management of overdose or unintentional ingestion, contact a Poison Control center (see Poison Control Center Listing ).Treatment of overdose

For acetaminophen:
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage.

Removing activated charcoal (if used) by gastric lavage may be advisable. Although activated charcoal is recommended in cases of mixed drug overdose, it may interfere with absorption of orally administered acetylcysteine (antidote used to protect against acetaminophen-induced hepatotoxicity) and decrease its efficacy.

To enhance elimination—Instituting hemodialysis or hemoperfusion to remove acetaminophen from the circulation may be beneficial if acetylcysteine administration cannot be instituted within 24 hours following ingestion of a massive acetaminophen overdose. However, the efficacy of this treatment in preventing acetaminophen-induced hepatotoxicity is not known.

Specific treatment—Administering acetylcysteine. It is recommended that acetylcysteine administration be instituted as soon as possible after ingestion of an overdose has been reported, without waiting for the results of plasma acetaminophen determinations or other laboratory tests. Acetylcysteine is most effective if treatment is started within 10 to 12 hours after ingestion of the overdose; however, it may be of some benefit if treatment is started within 24 hours. See the package insert or Acetylcysteine (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Determining plasma acetaminophen concentration at least 4 hours following ingestion of the overdose. Determinations performed prior to this time are not reliable for assessing potential hepatotoxicity. Initial plasma concentrations above 150 mcg per mL at 4 hours, 100 mcg per mL at 6 hours, 70 mcg per mL at 8 hours, 50 mcg per mL at 10 hours, 20 mcg per mL at 15 hours, 8 mcg per mL at 20 hours, or 3.5 mcg per mL at 24 hours postingestion indicate possible hepatotoxicity and the need for completing the full course of acetylcysteine treatment. If the initial determination indicates a plasma concentration below those listed at the times indicated, cessation of acetylcysteine therapy can be considered. However, some clinicians advise that more than one determination should be performed in order to ascertain peak absorption and half-life of acetaminophen prior to considering discontinuation of acetylcysteine.

Performing liver function tests (serum aspartate aminotransferase [AST or SGOT], serum alanine aminotransferase [ALT or SGPT], prothrombin time, and bilirubin) at 24-hour intervals for at least 96 hours postingestion if the plasma acetaminophen concentration indicates potential hepatotoxicity. If no abnormalities are detected within 96 hours, further determinations are not needed.

For opioid analgesics:
To decrease absorption—Emptying the stomach by induction of emesis or gastric lavage. However, treatment of respiratory depression or other potentially life-threatening adverse effects must take precedence.

Specific treatment—Administering the opioid antagonist naloxone. Larger doses of naloxone may be required to reverse the effects of pentazocine or propoxyphene than are required to antagonize the effects of other opioid analgesics. See the package insert or Naloxone (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Continuing to monitor the patient (mandatory because the duration of action of the opioid analgesic may exceed that of naloxone) so that additional antagonist may be administered as needed. Alternatively, initial treatment may be followed by continuous intravenous infusion of naloxone, with the rate of infusion being adjusted according to patient response. The fact that naloxone may also antagonize the analgesic actions of opioid analgesics and may precipitate withdrawal symptoms in physically dependent patients must be kept in mind.

Supportive care—Establishing adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled respiration.

Administration of intravenous fluids, vasopressors, and other supportive measures as needed. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Narcotic Analgesics and Acetaminophen (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):Before using this medication» Conditions affecting use, especially:Sensitivity to acetaminophen or to opioid analgesic considered for use, history of

Pregnancy—Acetaminophen and opioid analgesics cross the placenta; regular use of opioids by pregnant women may cause physical dependence in the fetus and withdrawal symptoms in the neonate

Breast-feeding—Acetaminophen, codeine, and propoxyphene are distributed into breast milk

Use in children—Children up to 2 years of age are more susceptible to the effects of opioids, especially respiratory depression; also, children may be more likely to experience paradoxical CNS excitation during therapy

Use in the elderly—Geriatric patients are more susceptible to the effects of opioids, especially respiratory depressionOther medications, especially alcohol or other CNS depressants, monoamine oxidase inhibitors, tricyclic antidepressants, zidovudine, and naltrexoneOther medical problems, especially alcoholism (active or in remission), diarrhea caused by antibiotics or poisoning, asthma or other respiratory problems, hepatic disease, viral hepatitis, and severe inflammatory bowel diseaseProper use of this medication» Importance of not taking more medication than the amount prescribed because of danger of overdose and habit-forming potential of opioid analgesics; also, acetaminophen may cause liver damage with long-term or high-dose use

» Not increasing dose if medication is less effective after a few weeks; checking with physician
Missed dose (if on scheduled dosing): Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storagePrecautions while using this medication
Regular visits to physician to check progress during long-term or high-dose therapy

» Caution if other medications containing opioid analgesics or acetaminophen are used

» Avoiding use of alcohol or other central nervous system (CNS) depressants during therapy unless prescribed or otherwise approved by physician

Checking with your physician if you consume three or more alcohol-containing beverages per day; acetaminophen may increase the risk of liver damage

Not regularly taking aspirin or other salicylates or other nonsteroidal anti-inflammatory drugs concurrently, unless directed by physician or dentist

General Dosing Information
Opioid analgesics may depress respiration, especially in very young, elderly, very ill, or debilitated patients and those with respiratory problems. Lower doses may be required for these patients. However, elderly patients may also be more sensitive to the analgesic effects of these medications so that lower doses and/or longer dosing intervals may be sufficient to provide adequate analgesia.

Dosage of opioid analgesics should be individualized on the basis of the potency and duration of action of the specific agent used, the severity of pain, the condition of the patient, other medications given concurrently, and patient response.

Administration of acetaminophen concurrently with opioid analgesics provides additive analgesia and may permit lower doses of the opioid analgesic to be utilized.

Some clinicians recommend that patients in chronic severe pain receive opioid analgesics on a fixed dosage schedule in order that they remain free of pain rather than on an as needed basis after pain recurs.

Tolerance to many of the effects of opioid analgesics may develop with repeated administration. The first sign of tolerance is usually a decrease in the duration of effective analgesia. Patients who become tolerant to one of these agents may be partially cross-tolerant to the others.

If tolerance to the opioid analgesic component of the medication develops, more frequent dosing and/or an increase in dosage may be required. However, the analgesic efficacy of acetaminophen is subject to a ceiling effect; single doses larger than 1 gram may not provide additional therapeutic benefit. Also, for chronic use, the maximum recommended dose of acetaminophen is 2.6 grams per day; chronic ingestion of larger daily doses increases the risk of hepatotoxicity. Therefore, administration of supplemental opioid analgesic, or administration of an opioid analgesic and acetaminophen separately, may be required in order to achieve adequate analgesia in opioid-tolerant patients.

Psychological and physical dependence may occur with chronic administration of opioid analgesics; an abstinence syndrome may occur when these medications are discontinued. Gradual withdrawal may minimize the development of withdrawal symptoms following prolonged use.

ACETAMINOPHEN AND CODEINE

Summary of Differences

Category:
Codeine is an opioid agonist analgesic.

Indications:
Indicated for relief of mild to severe pain, depending on the dose of codeine.

Precautions:
Pregnancy—Hydrocodone teratogenic in animals in very high doses.

Breast-feeding—Not known whether hydrocodone is distributed into breast milk.

Side/adverse effects:
Hydrocodone is more likely than most other opioids to cause side effects associated with histamine release.

Oral Dosage FormsHYDROCODONE BITARTRATE AND ACETAMINOPHEN CAPSULESUsual adult dose
Analgesic
Oral, one capsule every four to six hours, as needed. Dosage may be increased to two capsules every six hours if necessary.

Usual adult prescribing limits
Analgesic
Eight capsules per 24 hours.

Usual pediatric dose
Dosage has not been established.Strength(s) usually available
U.S.—

HYDROCODONE BITARTRATE AND ACETAMINOPHEN TABLETS {02} USPUsual adult dose
Analgesic
Oral, 1 or 2 tablets containing 2.5 mg of hydrocodone bitartrate and 500 mg of acetaminophen every four to six hours; or

Oral, 1 tablet containing 5 mg of hydrocodone bitartrate and 500 mg of acetaminophen every four to six hours as needed, with dosage being increased to 2 tablets every six hours if necessary; or

Oral, 1 tablet containing 7.5 mg of hydrocodone bitartrate and 650 mg of acetaminophen every four to six hours as needed, with dosage being increased to 2 tablets every six hours if necessary; or

Oral, 1 tablet containing 7.5 mg of hydrocodone bitartrate and 750 mg of acetaminophen every four to six hours as needed; or

Oral, 1 tablet containing 10 mg of hydrocodone bitartrate and 650 mg of acetaminophen every four to six hours as needed {33}.

Usual adult prescribing limits
Up to 40 mg of hydrocodone bitartrate and 4 grams of acetaminophen in twenty-four hours.Usual pediatric dose
Dosage has not been established.Strength(s) usually available
U.S.—

Canada—
Not commercially available.Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.Auxiliary labeling:
• May cause drowsiness.
• Avoid alcoholic beverages.
• May be habit-forming.Note: Controlled substance in the U.S.

Revised: 05/21/2001

References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

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